High Osmolarity Extends Life Span in Saccharomyces cerevisiae by a Mechanism Related to Calorie Restriction

Abstract

Calorie restriction (CR) extends life span in many different organisms, including mammals. We describe here a novel pathway that extends the life span of Saccharomyces cerevisiae mother cells but does not involve a reduction in caloric content of the media, i.e., there is growth of yeast cells in the presence of a high concentration of external osmolytes. Like CR, this longevity-promoting response to high osmolarity requires SIR2, suggesting a common mechanism of life span regulation. Genetic and microarray analysis indicates that high osmolarity extends the life span by activating Hog1p, leading to an increase in the biosynthesis of glycerol from glycolytic intermediates. This metabolic shift likely increases NAD levels, thereby activating Sir2p and promoting longevity.

A.A.A. and M.K. contributed equally to this work.

We thank T. Kaeberlein for reading the manuscript, S. Lin and P. Park for providing strains and plasmids, and T. Galitski for his contributions in the development of microarrays and analytical software tools.

This work was supported by grants to L.G. from the National Institute of Health (NIH), The Ellison Medical Foundation, The Seaver Institute, and the Howard and Linda Stern Fund. G.R.F. is supported by grants from the NIH and is an American Cancer Society Professor of Genetics. A.A.A. is supported by the NIH Training Grant in Genomic Sciences, sponsored by the Biotechnology Process Engineering Center.